The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with exposure to pesticides and other agricultural exposures. The study is a collaboration of the National Cancer Institute, the National Institute of Environmental Health Sciences, and the US Environmental Protection Agency, with additional collaboration by the National Institute for Occupational Safety and Health. We are examining cancer incidence and other health endpoints in a prospective study of licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Over a 3-year period (1993-7), we enrolled more than 57,000 licensed applicators, representing 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators also completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of farmer applicators enrolled and 2/3 of these also provided data on reproductive health, including information on all children under age 21. Since enrollment, 70% of participants completed the five-year followup phone interview (1999-2003) and the study achieved a similar response rate in our most recent followup phone interview (2005-2010). We are currently planning the next followup interview for FY13-14, to identify new cases of non-malignant outcomes and to update other factors that influence medical history. Annually, cancer incidence among the applicators, spouses, and children is determined through linkage with the population-based cancer registries in IA and NC. Follow-up computer-assisted telephone interviews are used to update exposure information, identify cases of non-malignant disease, and to collect information on changes in health status since enrollment in the study. We completed the second round of followup interviewing with cohort members in 2010. Buccal-cell samples have been collected from participants in order to extract DNA for future analyses of gene and environment interactions. In addition, a dietary assessment (food frequency questionnaire) was self-completed and returned by mail. In-depth assessment of agricultural exposures has been done for a small sample of farmers and their families in order to validate the questionnaires and facilitate exposure classification. Both environmental and biological samples were collected. Non-cancer outcomes of particular interest in this follow-up period include neurological diseases and symptoms (Parkinson's Disease, hearing loss, depression, neurobehavioral function, and suicide), respiratory and allergic outcomes (asthma, rhinitis, and chronic bronchitis), heart attacks (incidence and mortality), diabetes (both gestational and in adults), autoimmune diseases (rheumatoid arthritis, lupus, and Sjogren's syndrome), age-related macular degeneration, and birth outcomes (fertility, birthweight, pre-eclampsia) and reproductive outcomes (fibroids and endometriosis) in addition to cancer. We are currently involved in a number of substudies to collect more detailed information on potential health consequences of pesticides. In a collaboration with Frederic Gerr at the University of IA, we studied neurobehavioral function using a number of standardized tests for 701 farmers in the cohort. In this sample, high pesticide exposure events were associated with adverse CNS function and we saw no strong evidence of an association with organophosphate insecticide use and adverse CNS fuunction. Current analyses are focusing on peripheral nervous system function, depression, solvent exposure and other pesticides. The Growth and Puberty (GAP) Study is an intramurally-funded pilot study to assess the feasibility of measuring early puberty markers (hormone levels in urine and saliva, height velocity, Tanner staging) among farm children in the AHS. This study has enrolled approximately 60 children;sample and data analysis are ongoing. The Genes and Age Related Macular Degeneration (GENARM) Study is obtaining medical records, opthamalogical photographs, and saliva as a source of DNA for individuals who reported incident macular degeneration at one of the followup interviews. Field work is completed and data analysis is ongoing. Two more (Parkinson's disease and lung health) are described in separate annual reports. Recent results from the Agricultural Health Study include: 1) use of specific pesticides was associated with thyroid disease, particularly hypothryoid, in women;2) pesticides were associated with myocardial infarction incidence in women, but not men;3) farmers continue to have lower mortality risk, although after adjusting for this overall reduced risk, farmers and their spouses are at high risk of death of certain cancers;and 4) suicide risk for farmers is lower than that for the general population and there was no evidence of pesticide use contributing to suicide risk. The AHS cohort also participated in a number of large pooling studies that resulted in some important papers on BMI and mortality and BMI and pancreatic cancer. The Agricultural Health Study is one of the founding members of the Agricultural cohort consortium (AGRICOH) and we hope to use this collaboration to enhance our ability to assess rare exposures and outcomes, as well as gene-environment interactions. We continue to analyze data on farm exposures and non-cancer morbidity. Ongoing work focuses on patterns of pesticide use, endotoxin exposures, allergic and respiratory outcomes, reproductive outcomes, endocrine disorders, and neurological outcomes. Use of specific pesticides was associated with thyroid disease among farm women;we have just started the analysis of thyroid disease in men. Recent work also focuses on mortality in the cohort, specifically injury, stroke and kidney disease mortality. We are currently exploring agricultural factors associated with deaths from these causes. The most recent round of interviewing was completed in 2010 with the dataset available in 2011. With the newly collected data, we plan to conduct analysis of incident diseases such as asthma to expand on our earlier cross-sectional results. We have initiated a health followup study to validate self reports of diseases that may be inaccurate based on self-report;we are currently contacting individuals who reported autoimmune diseases (Rheumatoid arthritis, lupus, and Sjogren's syndrome) to confirm self-report, obtain medical records, and,for confirmed cases, collect a buccal cell for genetic analysis in the future.